Liquid storage container and cartridge

ABSTRACT

This invention relates to a cartridge (X) including at least one storage well ( 1 A- 1 E) which has an upper opening ( 1 A a - 1 E a ) and contains a liquid, at least one reaction well ( 2 A- 2 C) which has an upper opening ( 2 A a - 2 C a ) and provides a reaction field, and a closure (X 2 ) for closing the upper opening ( 1 Aa- 1 Ea) of at least the storage well ( 1 A- 1 E). At least one well ( 1 E) of the one or more storage wells and the reaction wells ( 1 A- 1 E,  2 A- 2 C) is provided with a adhering liquid mover ( 1 E b ) which downwardly moves liquid adhering on a peripheral portion of the upper opening ( 1 E a ) of the well ( 1 E) or on an inner surface of the well.

TECHNICAL FIELD

The present invention relates to a liquid storage container forcontaining liquid and a cartridge including a storage well holdingliquid.

BACKGROUND ART

An example of cartridge includes a disposable cartridge for immunoassay(refer to JP-A-2001-318101 for example). As shown in FIG. 12, acartridge 8 includes a plurality of wells 80-84 each encapsulating arespective reagent 80 a-84 a necessary for immunoassay. The cartridge 8also includes a plurality of cells 85-87 for optical check afterreaction of the reagent with a sample. The cartridge 8 utilizes areagent such as latex dispersion liquid. The latex dispersion liquid ismade by dispersing an immune reactant, which reacts selectively with aspecific component in the sample, in liquid as supported on by latexparticles. The wells 80-84 and the cells 85-87 include upper openings 80b-87 b which are closed by a seal 88, so that the reagents 80 a-84 a areprevented from spilling out when preserved. The reagents 80 a-84 a inthe cartridge 8 are all liquid. A pipette nozzle pierces the seal 88 andis inserted into the wells 80-84 to take out the reagents 80 a-84 a.

The cartridge 8 is generally stored or transferred in a manner such thatthe seal 88 is placed at the upside. However, a user may turn thecartridge upside down, or a shock or oscillation may be applied duringtransfer, so that the liquid surfaces of the reagents 80 a-84 a may beruffled. In such an instance, as shown in FIG. 13 illustrating the well84 for example, the reagent 84 a may adhere to the seal 88 or to aperipheral portion of the upper opening 84 b. The adhering reagent 84 a′may be removed by falling freely, but may also keep adhering to the seal88 due to the surface tension of the reagent 84 a′. As the adheringreagent 84 a′ cannot be easily taken out by the pipette nozzle, anusable amount of the reagent 84 a′ is substantially reduced once thereagent adheres as above-described. Therefore, considering the adhesionof the reagents 80 a-84 a, the amount of the reagents 80 a-84 a to besupplied in the wells 80-84 needs to be determined by adding a maximumamount of the reagents 80 a-84 a that may adhere. However, the reagentsuch as the latex dispersion liquid is so expensive that the amount usedmust be minimized in order to reduce the product cost.

As one solution to the above-described problem, as shown in FIG. 14, amedicine bottle 91 is provided with a stopper 90 which can be repeatedlypierced by a needle. The stopper 90 includes a hollow portion in which aspace 92 has a top portion 92a whose peripheral portion is preventedfrom adhesion of medicinal liquid (refer to JP-A-2002-535213 forexample). In this prior art, the stopper 90 is provided with grooves 93extending vertically for overcoming the surface tension of the medicinalliquid which adheres to the periphery of the top portion 92 a, therebyreturning the medicinal liquid back to the medicine bottle 91. However,when using the illustrated stopper 90, the medicinal liquid 95 mayadhere to the portion between an end 94 of the stopper 90 and themedicine bottle 91. Further, as the above-described cartridge 8 (seeFIG. 12) needs not be repeatedly pierced by a needle, the use of thestopper 90 is disadvantage in view of cost.

DISCLOSURE OF THE INVENTION

An object of the present invention is to prevent, advantageously in viewof cost, loss of usable liquid contained in a container in which theliquid keeps adhering to undesirable portions. For example, a cartridgefor containing a reagent is required to be initially filled with areduced amount of reagent, thereby preventing an increase of the productcost.

A first aspect of the present invention provides a liquid storagecontainer comprising: a receptacle for containing a liquid, thereceptacle including an upper opening; and a closure for closing theupper opening, wherein the receptacle is provided with an adheringliquid mover for moving the liquid, which adheres on a peripheralportion of the upper opening or on an inner surface of the container,toward a bottom of the receptacle.

A second aspect of the present invention provides a cartridgecomprising: at least one storage well including an upper opening andcontaining a liquid; at least one reaction well including an upperopening and providing a reacting field; and a closure for closing atleast the upper opening of the storage well, wherein at least one of thestorage well and the reaction well is provided with an adhering liquidmover which downwardly moves the liquid which adheres on a peripheralportion of the upper opening of the well or at an inner surface of thewell.

Preferably, the liquid to be contained in the container of the liquidstorage container or in the storage well of the cartridge comprises atleast one of a reagent, a diluent, and a cleaning solution.

Preferably, the reagent is necessary for causing immune reaction, andtypically, the reagent is made by dispersing an immune reactant, whichreacts selectively with a specific component in a sample, in liquid, assupported on solid particles.

Preferably, the closure comprises a sheet. There are a plurality ofstorage wells, and the sheet collectively covering the upper openings ofthe storage wells. The sheet may cover the upper openings of at leasttwo wells including the one or more storage well, out of the storagewell and the reaction well.

Preferably, the adhering liquid mover is provided on the inner surfaceof the receptacle of the liquid storage container, or the inner surfaceof at least one of the storage well and the reaction well of thecartridge.

For example, the adhering liquid mover comprises a notch, or preferably,a groove which is V-shaped in section. The adhering liquid mover mayalso be formed semicircular in section or rectangular in section, or maybe formed as a protrusion.

Preferably, the adhering liquid mover extends linearly, vertically, orspirally. Of course, the adhering liquid mover may extend obliquely.

Preferably, the adhering liquid mover is formed in a manner such that anupper end of the moving means contacts the closure. On the other hand,the adhering liquid mover is formed in the receptacle of the liquidstorage container or in at least one of the storage well and thereaction well of the cartridge, in a manner such that a lower end of themoving means is positioned below a surface of the liquid when thecontainer contains a desired amount of the liquid. Note that theadhering liquid mover is preferably formed such that the lower end doesnot contact the bottom surface of the container or of at least one ofthe well. Due to this structure, the adhering liquid is prevented fromremaining at the moving means when the liquid is taken out by a nozzle.

Preferably, the adhering liquid mover is formed by resin moldingintegrally with the receptacle of the liquid storage container or withat least one of the storage well and the reaction well of the cartridge.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front view illustrating an example of a cartridge accordingto the present invention.

FIG. 2 is a vertical sectional view illustrating the cartridge of FIG.1.

FIG. 3 illustrates the cartridge of FIG. 1 in an exploded perspectiveview and in an enlarged plan view.

FIG. 4 is a sectional view taken along lines IV-IV in FIG. 1.

FIG. 5 is a sectional view similar to FIG. 4, illustrating the functionof grooves formed in a storage well of the cartridge.

FIG. 6 is a sectional view similar to FIG. 2, illustrating an example ofmeasuring procedure utilizing the cartridge shown in FIGS. 13.

FIG. 7 is a sectional view similar to FIG. 2, illustrating an example ofmeasuring procedure utilizing the cartridge shown in FIGS. 1-3.

FIG. 8 is a sectional view similar to FIG. 2, illustrating an example ofmeasuring procedure utilizing the cartridge shown in FIGS. 1-3.

FIG. 9 is a sectional view similar to FIG. 2, illustrating an example ofmeasuring procedure utilizing the cartridge shown in FIGS. 1-3.

FIG. 10 is an enlarged plan view showing a principal part of thecartridge for illustrating another example of adhering liquid mover.

FIG. 11A is an enlarged plan view showing a principal part of thecartridge for illustrating still another example of adhering liquidmover, and FIG. 11B is a sectional view similar to FIG. 4, illustratingthe adhering liquid mover shown in FIG. 11A.

FIG. 12 is a sectional view illustrating an example of a conventionalcartridge.

FIG. 13 is an enlarged view illustrating a principal part of FIG. 12.

FIG. 14 is a sectional view illustrating a prior art method for removingadhering liquid.

BEST MODE FOR CARRYING OUT THE INVENTION

FIGS. 1-3 illustrate a cartridge X usable for measuring theconcentration of a target component in blood by latex agglutination. Thecartridge is set in a measuring instrument to cause a desired reaction.The cartridge X, which is disposable, includes a receptacle body X1 anda sealing member X2 fitted to the body X1.

The receptacle body X1 includes a plurality of storage wells 1A-1E, aplurality of reaction wells 2A-2C, a adjustment well 3, disposal well 4,a sample well 5, and a cuvette 6. The body X1 is formed to be entirelytransparent by molding using a transparent resin. Note that the body X1needs not necessarily be entirely transparent, if at least the reactionwells 2A-2C are transparent. The number, position and form of each ofthe wells 1A-1E, 2A-2C, 3-5 and the cuvette 6 are not limited to theillustrated example, but may be selected depending on the measurementtarget and measuring methods.

The storage wells 1A-1E contain reagents and so on (e.g. reagent,diluent, or cleaning liquid) necessary for measurement, and includeupper openings 1Aa-1Ea.

The storage well 1A contains a hemoglobin measuring reagent. Thehemoglobin measuring reagent is used for measuring the concentration ofhemoglobin in red blood cells, and any of various known reagents can beused if it reacts with hemoglobin to enable colorimetric measurementafter the reaction. The hemoglobin concentration is measured forcalculating the hematocrit value (volume percentage of red blood cellsin blood) based on the hemoglobin concentration, and for compensatingfor the influence of the hematocrit value on measurement.

The storage well 1B contains a hemolytic dilute solution. The hemolyticdilute solution is used for destructing blood cells to measure thecomponents contained in the blood cells. An example may be aphysiological saline solution containing saponin.

The storage well 1C contains an inert liquid usable as a diluent orcleaning solution. Any kind of inert liquid can be used if it does nothinder hemoglobin reaction or immune reaction of the measurement targetand does not cause errors in light absorbance measurement of hemoglobinand the measurement target. An example may be a physiological salinesolution or cattle serum albumin.

The storage well 1D contains a cleaning liquid. The cleaning liquid,which is distilled water in the present embodiment, is used for cleaninga pipette tip. Of course, other liquid than distilled water may be usedas the cleaning liquid.

The storage well 1E is formed with a plurality of grooves 1Eb andcontains a latex suspension. Each of the grooves 1Eb is V-shaped insection and extends vertically on the storage well 1E to serve as aadhering liquid mover. The groove 1Eb can be formed at the inner surfaceof the storage well 1E when forming the storage well 1E by molding. Aswell shown in FIG. 4, the groove 1Eb contacts the sealing member X2 atthe upper end, while contacting the latex suspension at the lower endpositioned below the surface of the latex suspension. With such anarrangement, as shown in FIG. 5, the groove 1Eb overcomes the surfacetension of the latex suspension deposited on the vicinity of the upperopening 1Ea and on the sealing member X2, and causes the depositinglatex suspension to drop along the groove 1Eb. In this way, it ispossible to prevent unexpected loss of the available latex suspension,thereby minimizing the amount of the latex suspension to be supplied tothe storage well 1E. As a result, a necessary amount of latex suspensionis reduced to lower the product cost.

The latex suspension may be prepared by dispersing an immune reactant,which reacts specifically to the measurement target component, in abuffer solution as supported on latex particles. Examples of themeasurement target component include disease markers such as hepatitisvirus, rheumatoid factor, C-reactive protein, hemolytic streptococcaltoxin, and various enzymes. The immune reactant may be selectedaccording to the types of the measurement target. The immune reactantprovides a specific antigen-antibody reaction with the above-describeddisease markers to agglutinate. An example of latex particles includeslatex beads of polystyren.

As shown in FIGS. 1-3, each of the reaction wells 2A-2C includes arespective upper opening 2Aa-2Ca. The reaction well 2A is used forpreparing a mixture liquid of diluted blood and the hemoglobin measuringreagent and for measuring the light absorbance of the mixture. In otherwords, the reaction well 2A is used for measuring the light absorbancenecessary for calculating the hemoglobin concentration. The reactionwell 2B is used for causing a latex agglutination reaction followed bymeasurement of the light absorbance. The reaction well 2C may be usedeither for measuring a target component different from that contained inthe reaction well 2B by causing an immune reaction different from thatoccurring in the reaction well 2B followed by measurement of the lightabsorbance, or for confirming the measurement repeatability by causingthe same immune reaction as the reaction well 2B followed by measurementof the light absorbance.

The adjustment well 3 is used for controlling blood and includes anupper opening 3A. The adjustment of blood may be performed by dilutingthe blood with the physiological saline solution contained in thestorage well 1C, for example.

The disposal well 4 is utilized for holding a pipette tip PT before useof the cartridge X. The disposal well is also used for disposing anunnecessary portion of liquid when using the cartridge X. The disposalwell 4 includes an upper opening 4 a and a shoulder 4 b for engaging thepipette tip PT. In use, the pipette tip PT is attached to a pipettenozzle PN (see FIG. 6A) for pipetting (sucking and discharging of liquidusing the pipette nozzle).

The sample well 5 is used for directly injecting the blood into the bodyX1. The cuvette 6 is used for setting a commercially available smalltube containing blood to the cartridge X. Selection between the samplewell 5 and the cuvette 6 depends on the structure of the measuringinstrument or on the choice by the user. In the latter case, themeasuring instrument may be designed to change in operational sequencefor enabling measurement regardless of which of the sample well 5 andthe cuvette 6 is selected for measurement. Further, the user operatesthe measuring instrument using e.g. a control button so that themeasuring instrument is able to distinguish which of the sample well 5and the cuvette 6 is used.

The sealing member X2 collectively seals the upper openings 1Aa-1Ea,2Aa-2Ca and 3 a of the wells 1A-1E, 2A-2C and 3 except the upper openingof the disposal well 4. However, the disposal well 4 may also be sealedtogether by the sealing member X2. The sealing member X2 is made of ametal foil such as aluminum foil or of a resin film, and can be easilypierced by the pipette tip. The sealing member X2 is fitted to the bodyX1 by using a hot-melt adhesive or by heat sealing.

As described above, the cartridge X is attached to the measuringinstrument for use. An example of measurement procedure utilizing thecartridge X is described below referring to FIGS. 6-9.

First, whole blood is supplied to the sample well 5 or to the cuvette 6of the cartridge X, and then the cartridge X is attached to themeasuring instrument (not shown). It should be noted that FIGS. 6-9illustrate an example where the sample well 5 holds the blood, and thefollowing description is given with respect to the example wherein wholeblood is held in the sample well 5.

The measuring instrument recognizes the attachment of the cartridge Xbased on a user's operation or automatically, for starting themeasurement process. The measurement process includes the concentrationmeasurement of hemoglobin and of the measurement target component.

As shown in FIG. 6A, the pipette tip PT is attached to the pipettenozzle PN before measurement. Specifically, the pipette nozzle PN of themeasuring instrument is moved, and the pipette tip PT held in thedisposal well 4 of the cartridge X is attached to the pipette nozzle PN.

Next, measurement of the hemoglobin concentration is performed. Thehemoglobin concentration measurement includes adjustment of sample,absorbance measurement, and calculation of the hemoglobin concentration(hematocrit value).

As shown in FIGS. 6A and 6B, in the sample adjustment, the physiologicalsaline solution in the storage well 1B is pippetted for dispensing intothe adjustment well 3. The physiological saline solution is pipettedtwice each by an amount of e.g. 95 μL for dispensing a total amount of190 μL into the adjustment well 3.

Thereafter, as shown in FIG. 7A, the inert liquid in the storage well 1Cis dispensed into the reaction well 2B. The inert liquid is pipettedonce by amount of e.g. 84μL for dispensing into the reaction well 2B.Then, as shown in FIG. 7B, the hemoglobin measuring reagent in thestorage well 1A is dispensed into the reaction well 2A. The hemoglobinmeasuring reagent is pipetted twice each by an amount of e.g. 77 μL fordispensing a total amount of 154μL into the reaction well 2A.Subsequently, the pipette tip PT is cleaned according to the steps shownin FIG. 7C. Specifically, the pipette tip PT is cleaned by sucking anddischarging the physiological saline solution in the storage well 1Btwice each by an amount of e.g. 110 μL, followed by transferring 50 μLof distilled water from the storage well 1D to the disposal well 4.

Next, as shown in FIG. 8A, the blood in the sample well 5 is dispensedinto the adjustment well 3 for dilution of the blood by mixing with theliquid in the adjustment well 3. The blood is pipetted once by an amountof e.g. 28 μL for dispensing into the adjustment well 3, and then themixing of the liquid in the adjustment well 3 is performed by suckingand discharging the liquid five times each by an amount of e.g. 110 μL.Subsequently, as shown in FIG. 8B, the pipette chip PT is cleaned byperforming the same steps as those described referring to FIG. 7C.Finally, as shown in FIG. 8C, the diluted blood in the adjustment well 3is dispensed into the reaction well 2A for mixing with the liquid in thereaction well 2A, whereby a final sample ready for hemoglobinconcentration measurement is prepared. The diluted blood is pipettedonce by an amount of e.g. 28 μL for dispensing into the reaction well2A, and then the mixing of the liquid in the reaction well 2A isperformed by sucking and discharging the liquid five times each by anamount of e.g. 110 μL.

In the absorbance measurement, a side of the reaction well 2A isirradiated with monochromatic light and the amount of light passingthrough the reaction well 2A is measured. The monochromatic light isselected according to the type of the hemoglobin measuring reagent. Forexample, light having a wavelength of 540 nm may be used. Thecalculation of the hemoglobin concentration is performed by substitutinga difference between a reference absorbance and the measured absorbanceinto a known equation. Based on the hemoglobin concentration obtained inthis way, the hematocrit value can be calculated. However, thehematocrit value can also be calculated directly based on the measuredabsorbance, without calculating the hemoglobin concentration.

After completing the measurement of the hemoglobin concentration(hematocrit value), the above-described concentration measurement of themeasurement target component is performed. The concentration measurementof the measurement target component includes sample adjustment,absorbance measurement, and concentration calculation.

As shown in FIG. 9A, in the sample adjustment, the pipette chip PT iscleaned by performing the same steps as those described referring toFIG. 7C. Thereafter, as shown in FIG. 9B, the diluted blood in theadjustment well 3 is dispensed into the reaction well 2B for mixing. Thediluted sample is pipetted once by an amount of e.g. 28 μL fordispensing into the reaction well 2B, and then the liquid in thereaction well 2B is mixed by sucking and discharging the liquid fivetimes each by an amount of e.g. 85 μL.

Next, as shown in FIG. 9C, the pipette tip PT is cleaned using thedistilled water in the storage well 1D. The cleaning of the pipette tipis performed by sucking and discharging the distilled water in thestorage well 1D twice each by an amount of e.g. 110 μL, followed bytransferring the distilled water in the storage well 1D to the disposalwell 4 by an amount of e.g. 110 μL. Finally, as shown in FIG. 9D, thelatex suspension in the storage well 1E is dispensed into the reactionwell 2B for mixing with the liquid in the reaction well 2B. The latexsuspension is pipetted once by an amount of e.g. 28.2 μL for dispensinginto the reaction well 2B, and then the liquid in the reaction well 2Bis mixed by sucking and discharging of the liquid three times each by anamount of e.g. 110 μL.

In the absorbance measurement, a side of the reaction well 2B isirradiated by monochromatic light and the amount of light passingthrough the reaction well 2B is measured. The monochromatic light isselected according to the measurement target component and the immunereactant held in the latex suspension. The calculation of theconcentration is performed by substituting a difference between areference absorbance and the measured absorbance into a known equation.The concentration of the measurement target component calculated in thisway is corrected based on the hematocrit value which has been previouslyobtained.

In the present embodiment, the storage well 1E alone is formed with thegrooves 1Eb (see FIG. 3 and 4), which are V-shaped in section, as theadhering liquid mover. However, the present invention is not limited tosuch a structure. For example, in place of, or in addition to thestorage well 1E, the other storage wells 1A-1D or the reaction wells2A-2C may be provided with an adhering liquid mover. Further, thestructure of the adhering liquid mover is not limited to the one shownin FIGS. 3 and 4. The adhering liquid mover may be formed as grooves 1Ebwhich are semicircular in section as shown in FIG. 10B, or may be formedas grooves 1Eb which are rectangular in section as shown in FIG. 10B.The adhering liquid mover may also be formed as a groove 1Eb′ extendingspirally as shown in FIGS. 11A and 11B, or a groove (not shown)extending obliquely. Of course, the adhering liquid mover maybe formedas a projection.

The present invention is applicable not only to an example using bloodas a sample, but also to a cartridge for analyzing other sample such asurine or saliva, or a liquid storage container for preserving liquids(including a sample).

1. A liquid storage container comprising: a receptacle for containing aliquid, the receptacle including an upper opening; and a closure forclosing the upper opening, wherein the receptacle is provided with anadhering liquid mover for moving the liquid, which adheres on aperipheral portion of the upper opening or on an inner surface of thecontainer, toward a bottom of the receptacle.
 2. The liquid storagecontainer according to claim 1, wherein the closure comprises a sheet.3. The liquid storage container according to claim 1, wherein theadhering liquid mover is provided on the inner surface of thereceptacle.
 4. The liquid storage container according to claim 1, theadhering liquid mover comprises a notch.
 5. The liquid storage containeraccording to claim 4, the adhering liquid mover comprises a groove whichis V-shaped in section.
 6. The liquid storage container according toclaim 4, the adhering liquid mover extends linearly and vertically. 7.The liquid storage container according to claim 4, the adhering liquidmover extends spirally.
 8. The liquid storage container according toclaim 1, the adhering liquid mover is formed on the inner surface of thereceptacle in a manner such that an upper end of the adhering liquidmover contacts the closure.
 9. The liquid storage container according toclaim 1, the adhering liquid mover is formed on the inner surface of thereceptacle in a manner such that a lower end of the adhering liquidmover is positioned below a surface of the liquid when the containercontains a desired amount of the liquid.
 10. The liquid storagecontainer according to claim 1, the adhering liquid mover is formedintegrally with the receptacle by resin molding.
 11. A cartridgecomprising: at least one storage well including an upper opening andcontaining a liquid; at least one reaction well including an upperopening and providing a reacting field; and a closure for closing atleast the upper opening of the storage well, wherein at least one of thestorage well and the reaction well is provided with an adhering liquidmover which downwardly moves the liquid which adheres on a peripheralportion of the upper opening of the well or at an inner surface of thewell.
 12. The cartridge according to claim 11, wherein the liquidcomprises at least one of a reagent, a diluent, and a cleaning solution.13. The cartridge according to claim 11, wherein the liquid comprises areagent.
 14. The cartridge according to claim 13, wherein the reagent isnecessary for causing immune reaction.
 15. The cartridge according toclaim 14, wherein the reagent is made by dispersing an immune reactant,which reacts selectively with a specific component in a sample, inliquid as supported on solid particles.
 16. The cartridge according toclaim 11, wherein the closure comprises a sheet.
 17. The cartridgeaccording to claim 11, wherein there are a plurality of storage wells,the sheet collectively covering the upper openings of the storage wells.18. The cartridge according to claim 11, wherein the sheet covers theupper openings of at least two wells including the storage well, out ofthe storage well and the reaction well.
 19. The liquid storage containeraccording to claim 11, wherein the adhering liquid mover is provided onthe inner surface of at least one of the storage well and the reactionwell.
 20. The liquid storage container according to claim 11, theadhering liquid mover comprises a notch.
 21. The liquid storagecontainer according to claim 20, the adhering liquid mover comprises agroove which is V-shaped in section.
 22. The liquid storage containeraccording to claim 11, the adhering liquid mover extends linearly andvertically.
 23. The liquid storage container according to claim 11, theadhering liquid mover extends spirally.
 24. The liquid storage containeraccording to claim 11, the adhering liquid mover is formed on the innersurface of at least one of the storage well and the reaction well in amanner such that an upper end of the adhering liquid mover contacts theclosure.
 25. The liquid storage container according to claim 11, theadhering liquid mover is formed on the inner surface of at least one ofthe storage well and the reaction well in a manner such that a lower endof the adhering liquid mover is positioned below a surface of the liquidwhen the container contains a desired amount of the liquid.